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解读肺动脉高压的复杂性:单细胞组学的新兴作用

Deciphering the Complexities of Pulmonary Hypertension: The Emergent Role of Single-Cell Omics.

作者信息

Rafikov Ruslan, de Jesus Perez Vinicio, Dekan Aleksandr, Kudryashova Tatiana V, Rafikova Olga

机构信息

Indiana University School of Medicine, Indianapolis, Indiana, United States;

Stanford University, Medicine, Stanford, California, United States.

出版信息

Am J Respir Cell Mol Biol. 2024 Aug 14;72(1):32-40. doi: 10.1165/rcmb.2024-0145PS.

Abstract

Expanding upon the critical advancements brought forth by single-cell omics in pulmonary hypertension (PH) research, this review delves deep into how these technologies have been piloted in a new era of understanding this complex disease. By leveraging the power of single cell transcriptomics (scRNA-seq), researchers can now dissect the complicated cellular ecosystem of the lungs, examining the key players such as endothelial cells, smooth muscle cells, pericytes, and immune cells, and their unique roles in the pathogenesis of PH. This more granular view is beyond the limitations of traditional bulk analysis, allowing for the identification of novel therapeutic targets previously obscured in the aggregated data. Connectome analysis based on single-cell omics of the cells involved in pathological changes can reveal a clearer picture of the cellular interactions and transitions in the cellular subtypes. Furthermore, the review acknowledges the challenges that lie ahead, including the need for enhancing the resolution of scRNA-seq to capture even finer details of cellular changes, overcoming logistical barriers in processing human tissue samples, and the necessity of integrating diverse omics approaches to fully comprehend the molecular underpinnings of PH. The promise of these single-cell technologies is immense, offering the potential for targeted drug development and the discovery of biomarkers for early diagnosis and disease monitoring. Through these advancements, the field moves closer to realizing the goal of precision medicine for patients with PH.

摘要

在单细胞组学为肺动脉高压(PH)研究带来的关键进展基础上,本综述深入探讨了这些技术如何在理解这一复杂疾病的新时代中得到应用。通过利用单细胞转录组学(scRNA-seq)的力量,研究人员现在可以剖析肺部复杂的细胞生态系统,研究诸如内皮细胞、平滑肌细胞、周细胞和免疫细胞等关键细胞类型,以及它们在PH发病机制中的独特作用。这种更细致的观点超越了传统批量分析的局限性,能够识别先前在汇总数据中被掩盖的新型治疗靶点。基于参与病理变化的细胞的单细胞组学进行的连接组分析,可以更清晰地呈现细胞亚型中的细胞相互作用和转变情况。此外,本综述认识到未来面临的挑战,包括需要提高scRNA-seq的分辨率以捕捉细胞变化的更细微细节、克服处理人体组织样本时的后勤障碍,以及整合多种组学方法以全面理解PH的分子基础的必要性。这些单细胞技术前景广阔,为靶向药物开发以及发现用于早期诊断和疾病监测的生物标志物提供了潜力。通过这些进展,该领域正朝着实现PH患者精准医学的目标迈进。

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